This Administrative Core will serve to coordinate the efforts ofthe three Projects and oversee the ufilizafion of the Core Facilifies to ensure that the goals of this Project are met. This Core will be located at the University of Chicago. The Program Director is Dr. Elizabeth McNally, a physician scienfist at the University of Chicago who is an expert in mouse modeling of muscular dystrophy. Dr. McNally also provides care to pafients with muscular dystrophy in the clinic she directs. Dr. McNally will direct Project 1 and lead this Administrafive Core A. The Project leaders are Dr. Se-Jin Lee, a Professor at Johns Hopkins, and Dr. Jeffrey Molkenfin, a Professor at the University of Cincinnati. Each of these investigators brings unique expertise and commitment to the study of muscular dystrophy. Dr. McNally has generated animal models of muscular dystrophy and idenfified the modifier gene Ltbp4. Dr. Lee discovered the myostafin pathway and its ability to regulate muscle growth. Dr. Molkenfin is expert in generafing mouse models with cardiac and muscle disease and has a longstanding interest in fibrosis. These three investigators have common interests, supported by collaborafion, and are uniquely posifioned to identify pathways and develop and test new therapies for muscular dystrophy. The outcomes from this Program will be: 1) Identify extracellular and intracellular events that regulate TGFp and myostatin processing and availability. 2) Discover the relafionship between muscle growth and muscle fibrosis mediated through TGFp and myostatin. 3) Realize new targets for therapy development including protease inhibitors, soluble receptors, decoy myostatin molecules and drugs to inhibit intracellular signaling pathways. To take advantage ofthe strengths ofthe three laboratories and three insfitufions requires regular communication, including videoconferencing, and face to face meefings throughout the year. Core A will coordinate communicafion, maintain and distribute up to date protocols, review Core utilization, oversee Project progress and coordinate review by the Internal and External Advisory Boards.